Cocaine evokes projection-specific synaptic plasticity of lateral habenula neurons.

Details

Serval ID
serval:BIB_95DEB8791D58
Type
Article: article from journal or magazin.
Collection
Publications
Title
Cocaine evokes projection-specific synaptic plasticity of lateral habenula neurons.
Journal
Journal of Neuroscience
Author(s)
Maroteaux M., Mameli M.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
32
Number
36
Pages
12641-12646
Language
english
Abstract
Addictive drugs share the ability to increase dopamine (DA) levels and trigger synaptic adaptations in the mesocorticolimbic system, two cellular processes engaged in the early stages of drug seeking. Neurons located in the lateral habenula (LHb) modulate the activity of DA neurons and DA release, and adaptively tune goal-directed behaviors. Whether synaptic modifications in LHb neurons occur upon drug exposure remains, however, unknown. Here, we assessed the influence of cocaine experience on excitatory transmission onto subsets of LHb neurons using a combination of retrograde tracing and ex vivo patch-clamp recordings in mice. Recent evidence demonstrates that AMPA receptors lacking the GluA2 subunit mediate glutamatergic transmission in LHb neurons. We find that cocaine selectively potentiates AMPA receptor-mediated EPSCs in LHb neurons that send axons to the rostromedial tegmental nucleus, a GABAergic structure that modulates the activity of midbrain DA neurons. Cocaine induces a postsynaptic accumulation of AMPA receptors without modifying their subunit composition or single-channel conductance. As a consequence, a protocol pairing presynaptic glutamate release with somatic hyperpolarization, to increase the efficiency of GluA2-lacking AMPA receptors, elicited a long-term potentiation in neurons only from cocaine-treated mice. This suggests that cocaine resets the rules for the induction of synaptic long-term plasticity in the LHb. Our study unravels an early, projection-specific, cocaine-evoked synaptic potentiation in the LHb that may represent a permissive step for the functional reorganization of the mesolimbic system after drug exposure.

Keywords
Animals, Cocaine/pharmacology, Female, Habenula/drug effects, Habenula/physiology, Male, Mice, Mice, Inbred C57BL, Neuronal Plasticity/drug effects, Neuronal Plasticity/physiology, Neurons/drug effects, Neurons/physiology, Synapses/drug effects, Synapses/physiology, Synaptic Potentials/drug effects, Synaptic Potentials/physiology
Pubmed
Web of science
Create date
31/01/2017 15:12
Last modification date
20/08/2019 14:58
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